scholarly journals Persistence of ribosomal protein synthesis after infection of HeLa cells by herpes simplex virus type 1.

1997 ◽  
Vol 78 (2) ◽  
pp. 435-443 ◽  
Author(s):  
D Simonin ◽  
J J Madjar ◽  
T Mass√© ◽  
J J Diaz
1996 ◽  
Vol 7 (2) ◽  
pp. 79-85 ◽  
Author(s):  
Kyoko Hayashi ◽  
Toshimitsu Hayashi

The antiviral activity of scopadulciol (SDC), a tetracyclic diterpenoid with a chemical structure related to that of aphidicolin, isolated from Scoparia dulcis, was studied in vitro against herpes simplex virus type 1 (HSV-1). SDC was found to inhibit the virus replication as shown by reduction of virus production. The action was not due to the inhibition of viral DNA polymerase activity and virus penetration, but might involve, at least in part, a virucidal effect. SDC did not suppress the viral protein synthesis of infected cells when added at an early stage of HSV-1 replication, but did when added later. When aciclovir (ACV) and SDC were evaluated in combination for antiviral activity against HSV-1 replication and cytotoxicity, these drugs inhibited viral replication in HeLa cells synergistically, but the same combination did not produce synergistic cytotoxicity in HeLa cells. Studies of the deoxynucleotide pool sizes revealed that SDC increased the intracellular dNTP pools and ACV triphosphate level significantly in infected cells when the cells were treated with the combination. These results could account for the synergistic action between SDC and ACV.


1995 ◽  
Vol 16 (1) ◽  
pp. 854-859 ◽  
Author(s):  
Denis Simonin ◽  
Jean-Jacques Diaz ◽  
Karine Kindbeiter ◽  
Luc Denoroy ◽  
Jean-Jacques Madjar

2001 ◽  
Vol 75 (11) ◽  
pp. 5189-5196 ◽  
Author(s):  
Ian Mohr ◽  
David Sternberg ◽  
Stephen Ward ◽  
David Leib ◽  
Matthew Mulvey ◽  
...  

ABSTRACT We describe here the neurovirulence properties of a herpes simplex virus type 1 γ34.5 second-site suppressor mutant. γ34.5 mutants are nonneurovirulent in animals and fail to grow in a variety of cultured cells due to a block at the level of protein synthesis. Extragenic suppressors with restored capacity to replicate in cells that normally do not support the growth of the parental γ34.5 deletion mutant have been isolated. Although the suppressor virus reacquires the ability to grow in nonpermissive cultured cells, it remains severely attenuated in mice and is indistinguishable from the mutant γ34.5 parent virus at the doses investigated. Repairing the γ34.5 mutation in the suppressor mutant restores neurovirulence to wild-type levels. These studies illustrate that (i) the protein synthesis and neurovirulence defects observed in γ34.5 mutant viruses can be genetically separated by an extragenic mutation at another site in the viral chromosome; (ii) the extragenic suppressor mutation does not affect neurovirulence; and (iii) the attenuated γ34.5 mutant, which replicates poorly in many cell types, can be modified by genetic selection to generate a nonpathogenic variant that regains the ability to grow robustly in a nonpermissive glioblastoma cell line. As this γ34.5 second-site suppressor variant is attenuated and replicates vigorously in neoplastic cells, it may have potential as a replication-competent, viral antitumor agent.


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